Acinetobacter spp. are widely distributed in nature. The genus Acinetobacter is divided into about 20 species. They are gram-negative, oxidase-negative, non-motile, nitrate-negative, non-fermentative bacteria.
Acinetobacter baumannii is the most frequently isolated species in this genus. They are able to survive on various surfaces (both moist and dry) in the hospital environment. A. baumannii has only recently been recognized as a nosocomial pathogen. Invasive techniques such as surgery, and pulmonary ventilation combined with immunocompromized patients, have led to the increased importance of the Acinetobacter genus as nosocomial pathogens.
The frequencies of both nosocomial and community-acquired infections have increased steadily over the years. In addition, treatment of these infections has become more challenging due to the emergence of (multi)-drug resistant strains.
Acinetobacter infections are usually diagnosed through symptoms for aerobic bacterial infections in combination with microbial cultures of body fluids originating from the infected tissue. The cultured bacteria are then identified in vitro. A variety of genotypic methods has been explored and applied to investigate the diversity or phylogeny in the genus. These methods include high-resolution fingerprinting with AFLP, PCR-RFLP with digestion of PCR amplified sequences, and analysis of various DNA sequences.
One of the most important developments in recent medical history is the development of vaccines which provide prophylactic protection from a wide variety of pathogenic organisms. Many vaccines are produced by inactivated or attenuated pathogens which are injected into an individual. The immunized individual responds by producing both a humoral (antibody) and cellular (cytolytic and/or helper and/or regulatory T cells etc) response.
However the use of attenuated organisms in vaccines for certain diseases is problematic due to the lack of knowledge regarding the pathology of the condition and the nature of the attenuation. An alternative to the use of inactivated or attenuated pathogens is the identification of pathogen epitopes to which the immune system is particularly sensitive. In this regard many pathogenic toxins produced by pathogenic organisms during an infection are particularly useful in the development of vaccines which protect the individual from a particular pathogenic organism.
A so-called subunit vaccine presents an antigen to the immune system without introducing pathogenic particles, such as viruses, whole or otherwise. Mostly such subunit vaccines are produced by recombinant expression of an antigen in a host organism, purification from the host organism and preparation of a vaccine composition.
In general, Acinetobacter species are considered nonpathogenic to healthy individuals. The recently recognized clinical importance of Acinetobacter species has stimulated interest in understanding the various bacterial and host components involved in the pathogenesis of these diseases. The knowledge of the interaction plays an important role in controlling the infection. Acinetobacter infections usually involve organ systems that have a high fluid content (e.g. respiratory tract, CSF (cerebrospinal fluid), peritoneal fluid, urinary tract), manifesting as nosocomial pneumonia, infections associated with continuous ambulatory peritoneal dialysis (CAPD), or catheter-associated bacteriuria.
Pantophlet et al. describe 0 antigens of Acinetobacter lipopolysaccharides (LPS) and corresponding antibodies for identification of Acinetobacter isolates (Pantophlet R. et al., Clinical and Diagnostic Laboratory Immunology, 9, 60-65 (2002)).
Tomarasz et al. identified the polycistronic csuAB gene cluster and showed its importance in the production and assembly of pili as well as in the subsequent formation of biofilms, e.g. on hospital surfaces and medical devices (Tomarasz A. P. et al., Microbiology, 154, 3398-3409 (2008)).
U.S. Pat. No. 6,562,958 discloses about 4000 nucleic acid and amino acid sequences relating to A. baumannii, however, they are mostly with unidentified function. U.S. Pat. No. 6,713,062 discloses OmpA and OmpA like protein being capable of stimulating gastrin and IL-8 gene expression.
However, no vaccines were developed as of today. Vaccines based on surface-exposed and secreted proteins against Acinetobacter infections have not been developed yet due to a lack of availability of feasible targets.
Therefore, there is a high medical need in the art for antigenic polypeptides expressed during an infection by Acinetobacter, preferably A. baumannii, and which are suitable for vaccine development and which are feasible for production of diagnostic, prophylactic and therapeutic antibodies.
A number of methods have been developed to identify potential antigenic polypeptides from various pathogens, however, they do not provide a general tool to prove the suitability of such polypeptides as immunogenic target in a vaccine composition.
Accordingly, the technical problem underlying the present invention is to provide clinically prevalent A. baumannii targets to be used in a vaccine composition and/or for production of diagnostic, prophylactic and therapeutic valuable antibodies.
The technical problem is solved by the provision of nucleic acids encoding antigenic polypeptides and antibodies or antibody-binding fragments that bind the antigenic polypeptides.